Effect of the New Antiepileptic Drug Levetiracetam in an Animal Model of Mania.

The new antiepileptic drug levetiracetam (LEV, Keppra) was evaluated in a putative animal model for mania, namely, dexamphetamine-chlordiazepoxide mixture-induced hyperactivity in rats submitted to a Y-shaped maze test. Lithium chloride, sodium valproate, and carbamazepine, all clinically effective drugs in the treatment of acute mania, were used as comparators. The results indicate that the clinical references significantly attenuated the mixture-induced hyperactivity, thus confirming the sensitivity and pharmacological validity of this model. LEV also significantly attenuated the mixture-induced hyperactivity at doses within the range of those reported to be active in epilepsy models. ucb L060, the R-enantiomer of LEV, was without effect, thus indicating that the "antimanic" activity of LEV is stereospecific. These results suggest a potential for LEV in the treatment of mania and possibly in the management of bipolar disorder.